Goals of this project are to improve clinical laboratory methods for diagnosis of disease. Studies include analysis of clinical laboratory practices, analysis of the accuracy of laboratory tests, and development of new tests and testing technologies. The data from a national survey of laboratory practices for measurement of parathyroid hormone during surgery on parathyroid glands was evaluated and published. Data was evaluated from a multicenter evaluation of the performance of glucose meters used by diabetics to measure their blood sugar levels. The study provides one of the most extensive evaluations of the consistency and accuracy of blood glucose meters. This will be useful for establishing goals for the performance of glucose meters and suggests approaches for improving their accuracy. Results are in press. A variety of new approaches have been developed for diagnosis of kidney disease. These recent developments were reviewed in a published editorial and ongoing research is seeking to improve the measurement of creatinine and to improve the diagnosis of kidney by laboratory methods. Mass spectrometry methods are under evaluation as a new approach for analysis of blood and urine specimens. Matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass spectrometry serves as a method for analysis of complex patterns of proteins and peptides in biological fluids. Results of our studies suggest that this method will be useful for study of a number of the small protein components of high-density and low-density lipoproteins (HDL and LDL). These studies may provide new insights into the structure of HDL and LDL that are commonly measured in the laboratory to assess risk for cardiovascular disease. These studies may also identify new technologies that can be applied for routine diagnostic methods. Ongoing studies are examining the interactions of the amino acid homocysteine with plasma proteins in extension of previous published studies that have examined relationships between homocysteine, cysteine, and plasma proteins. Increased concentrations of homocysteine are related to heart disease and abnormal formation of blood clots so there is a need for better understanding of interactions of this amino acid. Other studies have been directed at improving the measurement of the activity of proteases that are involved in many important processes such as blood coagulation. New reagents have been developed for measuring protease activity.